This proposal describes the development of a new class of biosensors exploiting an intrinsic property of DNA: electrical conduction. The capability of dsDNA to conduct electricity, in combination with the ability to measure this conduction in short (<100bp) and specific DNA sequences, will be harnessed to produce sensors with unprecedented sensitivity and portability. Conventional methods of detecting sequences on DNA arrays employ optical detection, and lack the sensitivity required to detect microbial species in clinical samples without extensive processing. The goal of this project is to construct a nanoscale DNA sensor with electrical detection that can sensitively and accurately detect Helicobacter pylori, a bacterium associated with gastric ulcers and cancer, in clinical samples. The specific aims of this project include (1) the demonstration of proof-of-principle for electrical DNA sensing carried out with synthetic DNA molecules modeling a unique H. pylori gene, and (2) the detection of H. pylori in clinical samples using electrical DNA detection.